QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 25, 2009, 29(8):2334-2343; doi:10.1523/JNEUROSCI.2296-08.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, S. Articles by Xiong, Z.-Q. Search for Related Content PubMed PubMed Citation Articles by Li, S. Articles by Xiong, Z.-Q.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
TORC1 Regulates Activity-Dependent CREB-Target Gene Transcription and Dendritic Growth of Developing Cortical Neurons

Shuai Li,¹ Chi Zhang,¹ Hiroshi Takemori,² Yang Zhou,¹ and Zhi-Qi Xiong¹

¹Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and ²Laboratory of Cell Signal and Metabolism, National Institute of Biomedical Innovation, Saito, Ibaraki, Osaka 567-0085, Japan

Correspondence should be addressed to either Dr. Yang Zhou or Dr. Zhi-Qi Xiong, Institute of Neuroscience, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China, Email: yzhou{at}ion.ac.cn or Email: xiongzhiqi{at}ion.ac.cn

CREB-target gene transcription during neuronal excitation is important for many aspects of neuronal development and function, including dendrite morphogenesis. However, the signaling events that regulate cAMP response element-binding protein (CREB)-mediated gene transcription during dendritic development are not well understood. Herein we report that the CREB coactivator TORC1 (transducer of regulated CREB 1) is required for activity-dependent CREB-target gene expression and dendrite growth in developing cortical neurons. Ca²⁺ influx via voltage-gated calcium channels induced TORC1 dephosphorylation and translocation into the nucleus in a calcineurin-dependent manner. Nuclear accumulation of TORC1 initiated the expression of CREB-target genes, including salt-inducible kinase 1 (SIK1). In response of persistent depolarization, de novo SIK1 protein in turn promoted TORC1 phosphorylation and consequent depletion of nucleus-localized TORC1. SIK1 induction thus appears to act as a negative feedback signal that prevents persistent CREB/TORC1-dependent transcription in the face of long-lasting neuronal activity. Overexpressing wild type TORC1 promoted basal as well as activity-induced dendritic growth, whereas expressing a dominant-negative form of TORC1 or downregulating TORC1 inhibited activity-dependent dendritic growth in vitro and in vivo. Together, these results suggest that neuronal activity-dependent dendritic growth in developing cortical neurons relies on transient TORC1-mediated CREB-target gene transcription.

Key words: activity; CREB; dendritic arborization; gene; transcription; development

---

Received May 21, 2008; revised Jan. 20, 2009; accepted Jan. 21, 2009.

Correspondence should be addressed to either Dr. Yang Zhou or Dr. Zhi-Qi Xiong, Institute of Neuroscience, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China, Email: yzhou{at}ion.ac.cn or Email: xiongzhiqi{at}ion.ac.cn

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2009 29: i. [Full Text]  

This article has been cited by other articles:

				M. Nonaka A Janus-Like Role of CREB Protein: Enhancement of Synaptic Property in Mature Neurons and Suppression of Synaptogenesis and Reduced Network Synchrony in Early Development J. Neurosci., May 20, 2009; 29(20): 6389 - 6391. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help